BACKGROUND: TB preventative therapy (TPT) is crucial for reducing the burden of TB in endemic settings. We assessed stigma associated with TPT and the social groups from whom stigma was anticipated.METHODS: We conducted an anonymous cross-sectional survey of community-dwelling adults in rural South Africa. Descriptive statistics, exploratory factor analysis, χ² tests, Kruskal-Wallis tests, and Poisson regression were used to identify factors associated with TPT stigma.RESULTS: The mean age of the 104 participants was 35 years, 65% were female, and 26% had completed secondary school. The vast majority perceived stigma associated with TPT (71%; mean score 1.7, SD ± 1.4). Factor analysis identified a two-factor solution that explained 61.9% of the variance. Being single (P < 0.001), previously screened for TB (P = 0.04), worried about being infected by TB (P = 0.006), and interested in taking TPT (P = 0.01) were associated with higher perceived stigma scores. TPT stigma was perceived among 8%, 16%, and 66% of their family, friends, and other community members, respectively.CONCLUSION: The prevalence of TPT-related stigma in a rural South African community was high. Community members anticipated less stigma from family members compared to other social groups. Global expansion and implementation of TPT will require novel interventions, such as engaging patients´ families to support uptake and promote adherence.